Diminished inhibitory control has been associated with greater drug and alcohol use. Disinhibitory psychopathologies, including attention-deficit hyperactivity and antisocial personality disorder, have a high comorbidity with drug and alcohol abuse. Moreover, reduced inhibitory control is an important element in theoretical formulations of addictive disorders. Despite these associations, no studies have compared healthy individuals differing in inhibitory control in terms of either potential predisposing factors, or risk for drug abuse. In the proposed research, groups of healthy young men and women exhibiting three different levels of inhibitory control, as defined by the Constraint factor of the Multidimensional Personality Questionnaire, will be ascertained. The proposed research will evaluate in these groups aspects of inhibitory control that have been implicated in its relationship to risk for drug abuse, including response inhibition (or impulsivity), novelty response, boredom susceptibility, and reward sensitivity. The P300 component of the event-related brain potential, an established marker of risk, will be elicited in a battery of cognitive tasks, and evaluated before and after administration of placebo and 10 mg d-amphetamine. The effects of a monetary incentive on P300 and performance will also be evaluated. In each session, subjective effects will be assessed before and after capsule administration, and a gambling task will be administered at the end of the session. It is hypothesized that highly disinhibited men and women will exhibit poorer response inhibition, a larger novelty response, and greater susceptibility to boredom. This group will also exhibit greater attention-enhancing effects of amphetamine and incentives, and will be more likely to exhibit a decision bias in favor of short- term rewards despite long-term losses in the gambling task. Finally, confirming the relationship between inhibitory control and risk, highly disinhibited participants will report more drug and alcohol use, and have a greater proportion of biological relatives who meet criteria for addictive and externalizing disorders. Thus, the proposed research will use psychometric and electrophysiological techniques to further define an elemental drug abuse phenotype-inhibitory control-and to confirm its status as a marker of vulnerability.